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A molecular model of the microsporidian infection apparatus

Project description

Visualising the unusual infection mechanism of tiny fungal pathogens

Tiny microsporidia are a growing threat to the global food supply chain, the environment, and human health. Classified as emerging pathogens of high priority, these unusual spore-forming organisms are opportunistic fungal pathogens that also pose challenges to drug development. To improve our understanding of the cell biological features that are central to microsporidian infectivity, the EU-funded PolTube project will develop a structural and mechanistic model of their infection apparatus, the polar tube. Specifically, it will use an innovative approach of cutting-edge structural biology techniques and newly developed in vivo tools to study the structure and function of the microsporidian polar tube. The result will be an architectural model of the invasion organelle, which will shed light on the unique evolutionary specialisation of these understudied organisms and provide novel tools for microsporidian research.

Objective

Microsporidia are opportunistic fungal pathogens that infect organisms as evolutionarily divergent as protists and mammals. Due to their growing impact on the global food supply chain, the environment, and human health, these unusual spore-forming organisms have been classified as emerging pathogens of high priority. Intriguing cell biological features that are central to microsporidian infectivity and pose challenges to drug development are poorly understood due to a lack of structural information and the absence of genetic tools. As energy parasites, microsporidia survive with the smallest eukaryotic genome and without classical mitochondria through an obligate intracellular lifestyle. A fascinating infection mechanism, which involves a long, hollow protein structure, is essential for efficient host invasion. The microsporidia-specific infection apparatus consists of several structural proteins that form the polar tube, which is used to inject the entire cytoplasm from the infectious spore into the host cell. Here, we will use an innovative approach to provide the structural and mechanistic basis of the microsporidian infection mechanism by using cutting-edge structural biology techniques and novel developed in-vivo tools. By studying the endogenous polar-tube, we will identify new elements and provide an architectural model of the invasion organelle. Reconstitution and biochemical characterization of the major components of the polar tube, followed by high-resolution cryo-EM studies, will unravel the polar tube protein interaction network and provide near-atomic information to complement the architectural model. Together with the development of genetic methods to tag, visualize and manipulate components in-vivo, we will provide a comprehensive model of the infection process, give insights into the specialization and evolution of a fascinating and understudied organism and deliver ground-breaking tools to open new frontiers in microsporidian research.

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Topic(s)

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ERC-STG - Starting Grant

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Call for proposal

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(opens in new window) ERC-2020-STG

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Host institution

UMEA UNIVERSITET
Net EU contribution

Net EU financial contribution. The sum of money that the participant receives, deducted by the EU contribution to its linked third party. It considers the distribution of the EU financial contribution between direct beneficiaries of the project and other types of participants, like third-party participants.

€ 1 500 000,00
Address
UNIVERSITETOMRADET
901 87 Umea
Sweden

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Region
Norra Sverige Övre Norrland Västerbottens län
Activity type
Higher or Secondary Education Establishments
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Total cost

The total costs incurred by this organisation to participate in the project, including direct and indirect costs. This amount is a subset of the overall project budget.

€ 1 500 000,00

Beneficiaries (1)

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